This grant proposal in a continuation of our previous work dealing with the psychopharmacology of the lithium ion. The scope has been considerably expanded; we now plan on concentrating our research efforts in using lithium as a tool to explore the biochemical framework underlying the affective disease entities. In this regard a number of studies are proposed exploring the metabolism of biogenic amines: determination of serum DBH activity; examination of MHPG, HVA, and 5HIAA in CSF; turnover rates add relative specific activities of NE3H2 as well as its major metabolites and biogenic amine transport in platelets. RBC COMT and the RBC/plasma lithium relationship is also proposed in distinguishing different clinical pictures. The effect of lithium on a variety of endocrines and the effects of this ion on the hypothalamus- pituitary axis will be explored; this includes thyroid and adrenocortical studies as well as further examination of carbohydrate metabolism. The lithium-aldosterone relationship will be examined with particular interest. Clinical studies will now concentrate on exploring lithium's potential therapeutic effects in other related disorders. These include aggressive/sociopathic behavior (prisoners), hyperactivity in adolescents and cyclic mood disturbances related to the menstrual cycle (pre-menstrual tension). Continuing to define a role for lithium in acute depressive recurrences is considered of central importance in considering lithium as an agent capable of affecting a disease entity rather than merely the symptoms of the related illnesses (i.e., the manic-depressive disorders).